Dopamine sudden depletion as a model for mixed depression.

Up to date research on Bipolar Disorders' phenomenology is in keeping with early descriptions made by E. Kraëpelin regarding the overlap in clinical presentation of both manic and depressive symptoms, namely, mixed states. The latter constitute a highly prevalent and characteristic clinical presentation of Bipolar Disorders' and entail therapeutic difficulties, prognostic implications and increased suicidal risk. Notwithstanding, mixed states', more specifically mixed depression, have been underestimated and bypassed to the point where currently neither diagnostic criteria nor specific therapeutic recommendations are provided. In addition to the lack of agreement on nosography and diagnostic criteria, mixed depression is usually excluded from Bipolar Disorders' neurobiological models. Furthermore, renewed interest in the role of dopamine in Bipolar Disorders' physiopathology has left aside hypothesis that may account for the aforementioned clinical presentation. Interestingly enough, other syndromes arising from sudden dopamine depletion such as neuroleptic dysphoria or withdrawal syndromes from dopaminergic drugs, bear remarkable clinical similarities with mixed depression. These syndromes have been subject of further research and may thus provide a model for mixed states' physiopathology. Indeed, this article accounts for clinical similarities between mixed depression, neuroleptic induced dysphoria, and other behavioural syndromes arising from sudden dopamine depletion. After reviewing neurochemical basis of such syndromes we present, to the best of our knowledge, the first neurobiological hypothesis for mixed depression. Specifically, such hypothesis regards over activation symptoms as auto regulatory attempts to compensate for sudden dopaminergic depletion. This hypothesis provides with a beginning step for the neglected problem of mixed depression, a non-antithetic link between the dopaminergic hypothesis for both manic and depressive symptoms, a plausible explanation regarding inter individual variability to mixed depression susceptibility, and suggests new approaches for the development of novel treatments in which dopamine dysregulation should be targeted.

Recombinant AAV-mediated delivery of a tet-inducible reporter gene to the rat retina.

Viral delivery of neurotrophins or other therapeutic genes is an attractive option for treating retinal degeneration. Regulated expression of these genes in the retina is needed to aid in dose delivery and to promote safety. To evaluate whether tetracycline (tet)-inducible transgenes encapsidated in recombinant adeno-associated viruses (rAAV) can provide controlled gene expression in vitro and in the rat retina, two viruses were constructed: a silencer/activator vector and an inducible doxycycline (dox)-responsive GFP vector. Combinations of these two viruses were subretinally injected into wild-type rats and dox was orally administered through the drinking water. Retinal GFP expression was monitored in vivo with a noninvasive fluorescence imaging method. Eyes were also examined by histology, Western analysis, and electroretinography. Subretinal injection of rAAV efficiently delivers inducible genes to both photoreceptors and retinal pigment epithelial cells. GFP expression was initially observed 1 week postinduction, and GFP protein was undetectable after removal of dox. In uninduced animals, GFP expression was negligible. The dox dosage was varied in vivo and showed a correlation to the level of GFP expression. Thus, transduction of retinal cells with tet-inducible vectors allows for tight regulation of gene expression.

[Coastal Chilean populations: genetic markers in four locations]. / Poblaciones costeras de Chile: marcadores genéticos en cuatro localidades.

BACKGROUND: Historical and anthropological data suggest the presence of descendents of Changos, Cuncos, Chonos and Yamanas, South American indian populations, in certain Chilean coastal villages. AIM: To assess the degree of South American indian admixture in Chilean coastal villages using protein markers, to complete the assessment of human biological diversity in Chile. SUBJECTS AND METHODS: ABO, Rh, MNS, Duffy and Kidd blood group systems were assessed in 47, 48, 55 and 24 individuals from Paposo, Carelmapu, Laitec and Ukika respectively. Phenotypic and gene frequencies were calculated. The degree of South American indian admixture was estimated from the ABO*O allele and Rh*dce haplotypes. RESULTS: High frequencies of ABO*O, Fy*a, Jk*b alleles, Dce and Ms haplotypes were found in all villages, consistent with the pattern expected for South American Aboriginal populations. The highest presence of South American indian admixture was present in Laitec with 80% and in Ukika with 74%. The figures for Paposo and Carelmapu were 60 and 65% respectively. CONCLUSIONS: According to South American indian admixture estimates, the genetic isolation of coastal populations is lower than that of inland subjects, suggesting that sea proximity facilitates gene flow.

Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery.

In vivo transduction of nondividing cells by human immunodeficiency virus type 1 (HIV-1)-based vectors results in transgene expression that is stable over several months. However, the use of HIV-1 vectors raises concerns about their safety. Here we describe a self-inactivating HIV-1 vector with a 400-nucleotide deletion in the 3' long terminal repeat (LTR). The deletion, which includes the TATA box, abolished the LTR promoter activity but did not affect vector titers or transgene expression in vitro. The self-inactivating vector transduced neurons in vivo as efficiently as a vector with full-length LTRs. The inactivation design achieved in this work improves significantly the biosafety of HIV-derived vectors, as it reduces the likelihood that replication-competent retroviruses will originate in the vector producer and target cells, and hampers recombination with wild-type HIV in an infected host. Moreover, it improves the potential performance of the vector by removing LTR sequences previously associated with transcriptional interference and suppression in vivo and by allowing the construction of more-stringent tissue-specific or regulatable vectors.

Chronic administration of amphetamine increases glutamic acid decarboxylase activity in the rat substantia nigra.

The glutamate decarboxylase activity in the rat cerebellum, frontal cerebral cortex, hypothalamus, substantia nigra and nucleus caudatus, was measured after either acute or chronic administration of (+)-amphetamine (1.35 and 5.4 mg/kg, i.p.). It was found that following 45 days of treatment the highest dose of the drug induced a selective increase of glutamate decarboxylase activity in the substantia nigra. Also in addition to the known changes in body weight, behavior and food-intake, some of the rats (5 out of 80 rats) treated with the highest dose of (+)-amphetamine developed a self-mutilating behavior. These results suggest that after the repeated administration of a high dose of (+)-amphetamine the activity of the striatonigral GABAergic pathway is increased and supports the idea that gamma-aminobutyric acid output neurons might convey dopamine-related functions.

Bloqueo de bronquio fuente izquierdo con cateter de Fogarty / Bronchial blocking left source with Fogarty catheter

Se considera de interés la presentación de este caso, por ser la primera vez que se emplea en nuestro medio el catéter de Fogarty como bloqueador bronquial en presencia de hemoptisis masiva durante la cirugía de resección pulmonar en el niño

Bloqueo de bronquio fuente izquierdo con cateter de Fogarty / Bronchial blocking left source with Fogarty catheter

Se considera de interés la presentación de este caso, por ser la primera vez que se emplea en nuestro medio el catéter de Fogarty como bloqueador bronquial en presencia de hemoptisis masiva durante la cirugía de resección pulmonar en el niño (AU)

[Superselective vagotomy of parietal cells. Evaluation and results in duodenal ulcer]. / La vagotomía superselectiva de celulas parietales. Evaluación y resultados en la ulcera duodenal.

The authors present a study carried out jointly by the Gastroenterology Service and Surgical Service No. 2 of the General Hospital of the Venezuela Institute of Social Security "Dr. Ildemaro Salas". The results and objectives of the operation are analyzed insisting on its lower morbility and mortality, as well as on the lower incidence of diarrhea, dumping and other gastrointestinales discomforts. The first operation was performed on 17 november 1971 and up to the present 74 patients have been operated, 65 for duodenal ulcers, 7 for esophageal hernia of the hiatus, 1 case of hemorrhagic gastritis, and 1 case of prepyloric ulcer. Some details are given of the operations, the indications for it are pointed out, specially gastric hyperacidity, symptomatic ulcer, and absence of duodenal stenosis. There were 7 post-operative complications and 2 cases of mortality. As to the results there are presented 92% successful interventions and 8% failures.